Project Summary/Abstract CAFETERIA Trial (Project 1) (ChAllenging to Foods with Escalating ThrEsholds for ReducIng Food Allergy). Food allergy affects up to 8% of children and approximately 5% of the adults, with serious consequences for quality of life and nutrition. Many current potential food allergy treatments under study address individuals who develop allergic reactions to very small amounts of the food, even trace amounts. However, not everyone with food allergy is exquisitely allergic. Based on studies of individuals undergoing diagnostic feeding tests, the majority experiencing allergic reactions develop symptoms after having ingested amounts that are often above an eighth of a teaspoon and usually much more. Currently, when a person with food allergy has an allergic reaction during a diagnostic feeding test, they are instructed to strictly avoid the food; this is standard clinical practice and is also a general instruction for anyone reporting allergic reactions to a food. Clinical care has not suggested, thus far, that allergic patients ingest ?sub-threshold? amounts of food allergen (amounts below those causing symptoms). However, the notion that strict avoidance could speed recovery of a food allergy has been entirely reversed by the results of studies of oral immunotherapy (giving initially trace amounts of an allergen and gradually increasing) and a new practice of having persons with egg or milk allergy ingest these foods in bakery goods if they are able (a finding identified by our group in a prior AADCRC grant that resulted in a worldwide change in practice). Both of these approaches have shown that ingestion of the allergen, if tolerated, appears to increase the threshold of reactivity and may speed recovery. Here we use peanut allergy as a prototype. Our hypothesis is that ingesting escalating sub-threshold amounts of peanut will be safe, increase threshold, and may speed recovery of peanut allergy. The study will enroll children shown to have moderate peanut allergy during a feeding test and randomize them to continue avoidance or to ingest a small but easily measurable amount of the food, an amount below that which causes symptoms. These children will undergo periodic supervised feeding tests to see if the amount can be increased, and will be compared to those following the current standard of care, avoidance. In addition, study participants will have bio-specimens obtained for evaluation in two additional Projects in this Program to understand mechanisms and biomarkers that can inform a personalized approach to peanut allergy. If this approach is successful, it will fundamentally change the worldwide approach to peanut allergy management, for perhaps the majority of affected individuals, and can be implemented easily by allergists.